Surfactant composition

ABSTRACT

The present invention relates to a surfactant composition comprising at least one alkylglycoside having the formula CnGm wherein C is an alkyl group; n is the number of carbon atoms in the alkyl group and is 14 to 24; said alkyl group being unbranched or branched, saturated or unsaturated, derivatised or non-derivatised; G is a saccharide residue containing 5 to 6 carbon atoms; and m is a number from 4 to 20. It further also relates to its use and application in detergents, emulsifying agents, wetting agents, anti-aggregation and stabilising composition and dispersants comprising the same.

TECHNICAL FIELD

The present invention relates to surfactant compositions and theirapplications.

BACKGROUND

Surfactants (surface active agents, also referred to as tensides) areubiquitous, and used in products and applications where it is necessaryto decrease the surface tension between two immiscible phases, or whereit is necessary to increase the solubility of one phase in the other.Normally, one of the phases consists of water or a water-rich mixture(the aqueous phase), whereas the other consists of a liquid or solidphase (the oily phase) that is, by itself, immiscible or poorly solublein water. Surfactants perform their action by adsorbing to the interfacebetween the aqueous and oily phase, and/or by spontaneously formingaggregates (e.g. liquid crystals or micelles). In order to do so, it isnecessary that the surfactant molecule consists of two separate, butlinked moieties; a hydrophilic moiety that is soluble in water (the“head-group”), and a hydrophobic moiety, that is soluble in oil (the“tail”). This dual nature of the molecule is referred to asamphiphilicity. The amphiphilic character of the surfactant moleculemeans that the hydrophilic part will prefer to dwell in the aqueousphase, whereas the hydrophobic part will prefer the oily phase.Consequently, the surfactant as a whole will prefer to reside at theinterface between the aqueous and the oily phase, hence decreasing thesurface tension between the two phases and facilitating mixing(dispersing) of one phase in the other. Another effect of the surfactantamphiphilicity is its capacity to spontaneously form aggregates. Inaqueous solution, soluble surfactants thus spontaneously formaggregates, micelles, where the hydrophobic moieties are directedinwards, away from the aqueous phase, whereas the hydrophilic moietiesare directed outwards, towards the aqueous phase. As a consequence, anoily substance can be incorporated in the interior, hydrophobic part ofthe micelles, hence increasing its solubility. This process is referredto as solubilisation, and the lowest surfactant concentration at whichmicelles form is referred to as the critical micelle concentration(CMC). The CMC is an important characteristic of a surfactant. Above theCMC all additional surfactants added to the system go to micelles.Before reaching the CMC, the surface tension changes strongly with theconcentration of the surfactant. After reaching the CMC, the surfacetension remains relatively constant or changes with a lower slope. Thevalue of the CMC for a given agent in a given medium depends ontemperature, pressure, and on the presence and concentration of othersurface active substances and electrolytes. Another importantcharacteristic of a surfactant is the so-called Krafft temperature. TheKrafft temperature is defined as the temperature at which the surfactantconcentration of the saturated surfactant solution equals CMC.Consequently, at temperatures below the Krafft temperature, thesurfactant solubility is very low and the surfactant behaves as aregular organic molecule. At the Krafft temperature the solubilityincreases dramatically, micelles form and the surface active propertiesof the surfactant manifest themselves in a useful manner. Attemperatures below the Krafft temperature, on the other hand, thesolubility of the surfactant is so low that the surfactant ispractically useless in many applications. As will be elaborated onbelow, most applications therefore require surfactants with Krafftpoints below room temperature, since products containing surfactants aregenerally intended for use under everyday conditions.

Both CMC and Krafft temperature depend directly on surfactant structure.Keeping other molecular properties constant, increasing alkyl chainlength decreases CMC and favors surfactant adsorption, whereasincreasing head-group length decreases the Krafft temperature. Thisdependence has direct practical consequences for surfactant selectionand design. As already described, it is of utmost importance to identifya surfactant that has a Krafft point well below the temperature to whichthe product will be subjected under actual use (normally roomtemperature). On the other hand, a long alkyl-chain promotes adsorptionand aggregation, so that a smaller concentration of surfactant isrequired to achieve a given effect. Consequently, a combination of along alkyl chain with a long head-group is often beneficial forsurfactant functionality.

The molecular characteristics of a given surfactant also directly impactits interactions with cells and mucosa, and hence its toxicologicalproperties. In this respect it is important to note that an inherentdrawback of the amphiphilic nature of surfactants is their tendency toadsorb to mucosal surfaces and other biointerfaces, as well as toincorporate themselves into cell membranes. Studies show that thetoxicity towards aquatic model organisms decreases with decreasingsurface activity and increasing size of the head-group^([18,19]). Theseconclusions have been shown to hold true also in human cell modelsM^([1]). Furthermore, the studies in human cell models have revealedthat a long alkyl chain is also, in itself, beneficial in terms ofbiocompatibility. Consequently, the combination of a long alkyl chainwith a long head-group is beneficial also in terms of toxicity. In moregeneral terms, the toxicological profile of non-ionic (charge-neutral)surfactants are superior as compared with anionic surfactants, which, inturn, are superior over cationic ones^([18,19]). For many applicationsthat require high biocompatibility, non-ionic surfactants are thereforethe prime choice.

In addition to the aspects pertaining to acute toxicity, the overallenvironmental impact of a surfactant is also an important factor toconsider when comparing different surfactants. Both the properties ofthe surfactant itself, such as biodegradability, and the properties ofthe manufacturing process, e.g. the nature of the starting materials,must be considered.

The amphiphilic nature of surfactants makes them act as detergents,wetting agents, emulsifiers, dispersants etc. Surfactants are thereforeused in manifold applications, e.g. pharmaceutics, food, paint,adhesives, personal care products, cosmetics, laundry and also for morespecialised applications like membrane protein solubilisation.

Dispersions of solid particles in a liquid aqueous medium are normallyreferred to as suspensions or sols. Such systems are essential in manyapplications, e.g. pigment particles in paints, and sun-blockingparticles in creams and lotions for cosmetic use. In order to properlywet and disperse the particles in suspensions a surfactant is generallyrequired in order to decrease the surface tension between the particleand the continuous medium. Similarly, proper dispersion of a liquid oilyphase in water (or dispersion of water in oil) is referred to asemulsification. Again, examples of emulsions include paint and cosmeticpreparations.

In the field of pharmaceutics, surfactants are used for e.g. suspensionof hydrophobic drug particles in aqueous media, for instance in liquidsfor inhalation (pulmonary nebulisation and nasal sprays); emulsificationof oily drugs in aqueous vehicle, for instance in creams and lotionscontaining pain-killers; and for inhibition of protein and peptideadsorption and aggregation in liquid formulations for injection andinhalation.

A particularly challenging application is pharmaceutics intended forpulmonary and nasal inhalation (liquids for nebulisation and nasalsprays). In order to have its desired effect, the drug particles ininhaled medications need to be micronised, i.e. milled to a size of afew microns. As a result of the small particle size, the powder becomesextremely cohesive and difficult to disperse. In addition, the drugparticles are often very hydrophobic and therefore difficult to wet. Asa consequence of these features, aggregation (i.e. formation of larger,composite particles, composed of primary particles) is oftenencountered. Aggregation is detrimental to product performance, sincelarger particles do not reach the deep parts of the pulmonary tract, dueto impaction and concomitant retention in airway bifurcations. Due tothe challenging demands on formulations for inhalation, it is generallytrue that a formulation concept that works in the area of inhalationalso works in other, less challenging pharmaceutical areas, such asdispersion of solid particles in topical creams and lotions as well asinjectabilia.

Preferably, a surfactant is chemically stable, i.e. does not readilydegrade under the intended product shelf life and does not inducedegradation of other components in the formulation. This is especiallyimportant for pharmaceutics, cosmetics and food, where a strictminimisation of degradents is desirable for reason of safety and productperformance.

Today, the field of non-ionic surfactants is completely dominated bysubstances based on the use of polyethyleneglycole (PEG, also referredto as polyethyleneoxide, PEO) as hydrophilic head-group. In simplePEG-chain surfactants, the PEG chain may be attached to the hydrophobicmoiety of the surfactant (the alkyl chain) trough an ester bond (e.g.Solutol™ and the Myrj™ family of surfactants) or an ether bond (e.g. theBrij™ family of surfactants). More complex PEG-based surfactants includethe well-known family of ethoxylated sorbitan esters known aspolysorbates (or Tween™), amphiphilic co-polymers of PEG andpoly(propylene oxide) (e.g. Pluronics™), and ethoxylated triglycerides(e.g. Cremophor™). Polysorbate is of particular interest, since it isthe only surfactant currently approved for all pharmaceuticaladministration forms.

In spite of the fact that they are produced and used on an enormousscale, all surfactants based on PEG share a number of substantialdrawbacks, namely formation of toxic degradation products in aqueoussystems (e.g. formaldehyde, formic acid and acetaldehyde); chemicalinstability and generation of oxidising peroxo radicals having adetrimental effect on product stability; polydispersity and batchvariability^([2-5]). Furthermore, the temperature-sensitivity of aqueoussolutions (phase separation, clouding, emulsification failure) is aproblem in processes that involve heat, such as e.g. sterilisation bymeans of autoclavation^([6]). In addition, most PEG-based surfactantshave petrochemical origin, thus not originating from renewable sources,which is important when considering the environmental impact of asurfactant.

Another group of non-ionic surfactants are the alkylglycosides, alsonamed alkylpolyglucosides, which are non-ionic surfactants derived fromsaccharides (sugars). These surfactants have been found to be compatiblewith skin and mucosa and to be non-toxic in acute and repeated dosetoxicity studies^([20]). Glycosides are substituted saccharides in whichthe substituent group is attached, through an oxygen atom, to analdehyde or ketone carbon. Accordingly, glycosides are consideredacetals. As with the term “saccharide”, the term “glycoside” definesneither the number nor the identity of the saccharide units in themolecule. A common shorthand nomenclature applied to alkylglycosides isC_(n)G_(m), where n is defined as the number of carbon atoms in thealkyl chain and m the number of saccharide units (normally glucoseunits) comprising the head group.

Alkylglycosides are known to be effective as surfactants in detergentsand they exhibit solubilizing properties. In addition, alkylglycosideshave a favourable biodegradability, with degradation products being analcohol or fatty acid and an oligosaccharide^([23]). In contrast to thePEG-based surfactants they are stable towards hydrolysis andautoxidation in aqueous systems, and do not give rise to toxicdegradation products, Hence, they have found use in many applicationswhere they come in contact with the human body, such as cosmetics andpersonal care products. Examples of alkylglycosides used today in theseapplications are EcoSense 1200 (alkylpoly glucoside C12-14) and EcoSense919 (alkylpoly glucoside C8-16) from Dow Chemicals, Plantaren (decylglucoside), Plantapon LGC Sorb (sodium lauryl glucose carboxylate),Plantasol CCG (caprylyl capryl glucoside) from Cognis, and TEGO CareCG90 (C16-C18 glucoside) from Evonik, etc. In the pharmaceutical field,Aegis Therapeutics has recently developed technologies primarilyutilizing C14G2 for enhancement of the physical stability andbioavailability of peptides and proteins^([21,22]).

Ways to produce alkylglycosides have previously beendisclosed^([8,9,10]).

Conventional, commercially available alkylglycosides, such as thosementioned in the preceding paragraph, address many of the issues relatedto PEG-based surfactants, but still have a number of drawbacks.Conventional Fischer synthesis, used for the industrial production ofthese alkylglycosides, yields a polydisperse mixture of alkylglycosideshaving only 1-3 repeating sugar units^([7]). With such shorthead-groups, it is not possible to extend the length of the tail withoutrisking problems related to high Krafft points and concomitant issuesrelated to poor solubility. As already described, the toxicity of asurfactant also increases with shorter head-group. Hence, there is aneed for a new type of surfactant that addresses these issues.

SUMMARY OF THE INVENTION

We have found that alkylglycosides C_(n)G_(m) with a long alkyl chain(n≧14) and long head-group (m≧4) indeed address these needs and alsobring other, unexpected benefits in terms of surfactant functionality.These novel alkylglycosides according to the present invention can beproduced by enzymatic means. Production of alkylglycosides using enzymeshas previously been disclosed in EP2401389A1. According to the presentinvention, depending on the choice of enzyme and reactants, theresulting alkylglycoside composition may have either of the followingtwo key characteristics:

(A). A binary mixture of C_(n)G_(m1) and C_(n)G_(m2), where m1 and m2 iseither 7 and 13, or 8 and 14. In the following, this type of binarysurfactant composition is referred to by the shorthand notationC_(n)G_(m1/m2). Thus, C_(n)G_(7/13) refers to a binary mixture ofC_(n)G₇ and C_(n)G₁₃, whereas C_(n)G_(8/14) refers to a binary mixtureof C_(n)G₈ and C_(n)G₁₄. For instance, this type of binary mixtures canbe produced using commercially available C₁₆G₂ as starting material,which yields C₁₆G_(8/14).

(B). A mixture of molecules C_(n)G₄, C_(n)G₅, . . . , C_(n)G₂₀. In thefollowing, this type of polydisperse surfactant composition is referredto by the shorthand notation C_(n)G₄₋₂₀. Thus, C₁₆G₄₋₂₀ refers to amixture of C₁₆G_(n) molecules with n in the range 4-20. For instance,this type of polydisperse mixture can be produced from a commerciallyavailable mixture of C₁₆G₁ and C₁₈G₁ (brand name TEGO Care CG16 fromEvonik), which yields C₁₆₋₁₈G₄₋₂₀.

The present invention relates to unique surfactant compositions based onalkylglycosides with hydrophilic head-groups consisting of four or morerepeating saccharide units. In contrast to existing alkylglycosidecompositions, the composition described herein contains alkylglycosideswith long head-groups (n≧4) as main components. The invention alsorelates to the use of the compositions as surface-active agentsparticularly in the field of wetting particles and surfaces,emulsification and stabilisation of pharmaceuticals.

The above mentioned problems described in the Background are solved withthe surfactant compositions according to the present invention.

According to one object the present invention relates to a surfactantcomposition comprising at least one alkylglycoside having the formula I

C_(n)G_(m)  (I)

whereinC is an alkyl group;n is the number of carbon atoms in the alkyl group and is 14 to 24;said alkyl group being unbranched or branched, saturated or unsaturated,derivatised or non-derivatised;G is a saccharide unit containing 5 to 6 carbon atoms; andm is a number from 4 to 20.

According to one embodiment the alkyl group comprises cyclic fractions.

According to one embodiment m is 4-19, preferably 4-18, preferably 4-17,preferably 4-16, preferably 4-15, or preferably 4-14.

According to another embodiment m is between 6 and 18, preferablybetween 7 and 17, more preferably is chosen from 7, 8, 13 or 14.

According to another embodiment n is 14 to 22, preferably 14 to 20,preferably 14 to 18, and more preferably 16 to 18.

According to another embodiment m is selected from 7, 8, 13, or 14; andn is selected from 16 or 18.

According to another embodiment the surfactant composition comprises atleast two alkylglycosides having m being 7 or 8 and 13 or 14,respectively.

According to another embodiment the ratio between (C_(n)G₈) to(C_(n)G₁₄) or (C_(n)G₇) to (C_(n)G₁₃) is about 50:50 to 95:5.

Polydisperse mixtures comprising these alkylglycosides are referred toas C_(n)G₄₋₂₀, in accordance with the nomenclature and definitionsdescribed previously. Preferred embodiments of a polydisperse mixturemay be disclosed as e.g. C_(n)G₄₋₁₉, C_(n)G₄₋₁₈ etc, in accordance withthe above mentioned embodiments.

Binary mixtures consistent with the above mentioned preferredembodiments may be referred to as e.g. C_(n)G_(8/14) and C_(n)G_(7/13),respectively, in accordance with the nomenclature and definitionsdescribed previously. Naturally other types of binary combinations mayalso be made within the scope of the present invention.

According to another embodiment the at least one alkylglycoside has asurface tension value at or above critical micelle concentration (CMC)of at least 32 mN/m, for example at least 40 mN/m, preferably 42-49mN/m, preferably about 45-49 mN/m, such as about 47 mN/m.

According to one object the present invention relates to a detergentcomposition comprising said surfactant composition.

According to one object the present invention relates to a wetting agentcomprising said surfactant composition.

According to one object the present invention relates to an emulsifyingagent comprising said surfactant composition.

According to one object the present invention relates to a dispersantcomposition comprising said surfactant composition.

According to one object the present invention relates to ananti-aggregation and stabilising composition comprising biomolecules andsaid surfactant composition.

According to one object the present invention relates to use of saidsurfactant composition as a detergent, a wetting agent, an emulsifyingagent, an anti-aggregation agent or a dispersant.

According to one object the present invention relates to use of saidsurfactant composition in foods, beverages, pharmaceuticals, cosmetics,personal care products, detergents or cleaning agents.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the tensiometric determination of the CMC of asurfactant composition comprising a C₁₆G_(8/14) mixture at roomtemperature.

FIG. 2 shows ellipsometric data on the adsorbed amount of a surfactantcomposition comprising a C₁₆G_(8/14) mixture on hydrophobic substrate(silica, hydrophobized with dimethyloctylchlorosilane). Theconcentration of the C₁₆G_(8/14) solution in each phase of theexperiment is displayed in the figure.

FIG. 3 shows the total BHT content as a function of time in systemsstored at 40° C. Solid squares denote the system in which a surfactantcomposition comprising a C₁₆G_(8/14) mixture was used as dispersant,whereas open circles and triangles denote systems containing polysorbateof super-refined and pharma grade, respectively. The error barsrepresent 1σ.

FIG. 4 shows data on particle size distributions of BDP dispersed byhigh-shear mixing in aqueous vehicles comprising a C₁₆G_(8/14) mixture(left hand panel), or comprising PS80 (right hand panel).

FIG. 5 shows data on particle size distributions of BDP dispersed bylow-shear mixing in aqueous vehicles comprising 0.2 mg/ml of aC₁₆G_(8/14) mixture (left hand panel), or comprising 0.2 mg/ml of PS80(right hand panel).

FIG. 6 shows aggregates of BDP primary particles, as characterised byFast Particle Image Analysis (FPIA) on a system containing 0.2 mg/ml ofPS80 as dispersant, and prepared by high-shear mixing.

FIG. 7 shows aggregates of BDP primary particles, as characterised byFPIA analysis on a system containing a surfactant composition comprising0.2 mg/ml of a C₁₆G_(8/14) mixture as dispersant, and prepared byhigh-shear mixing.

FIG. 8 shows aggregates of BDP primary particles, as characterised byFPIA analysis on a system containing 0.2 mg/ml of PS80 as dispersant andprepared by low-shear mixing.

FIG. 9 shows aggregates of BDP primary particles, as characterised byFPIA analysis on a system containing a surfactant composition comprising0.2 mg/ml of a C₁₆G_(8/14) mixture as dispersant and prepared bylow-shear mixing.

FIG. 10 shows laser diffraction data on suspensions of micronisedbudesonide (0.5 mg/ml), prepared with 0.2 mg/ml of C₁₆₋₁₈G₄₋₂₀ asdispersing agent.

FIG. 11 shows laser diffraction data on suspensions of micronisedbudesonide (0.5 mg/ml), prepared with 0.2 mg/ml of C₁₆₋₁₈G₁₋₃ asdispersing agent.

FIG. 12 shows laser diffraction data on suspensions of micronisedbudesonide (0.5 mg/ml), prepared with 0.2 mg/ml of TEGO Care CG90(C₁₆₋₁₈ G₁) as dispersing agent.

FIG. 13 shows laser diffraction data on suspensions of micronisedbudesonide (0.5 mg/ml), prepared with 0.2 mg/ml of Polysorbate 80 asdispersing agent. The top panel displays the particle size distributionof the suspension when freshly prepared. The middle panel displays theparticle size distribution after heating to 90° C. for 30 minutes. Thebottom panel displays the particle size distribution after autoclavationat 125° C. for 8 minutes.

FIG. 14 shows laser diffraction data on suspensions of micronisedbudesonide (0.5 mg/ml), prepared with 0.2 mg/ml of a C₁₆G_(8/14) mixtureas dispersing agent. The top panel displays the particle sizedistribution of the suspension when freshly prepared. The middle paneldisplays the particle size distribution after heating to 90° C. for 30minutes. The bottom panel displays the particle size distribution afterautoclavation at 125° C. for 8 minutes.

FIG. 15 shows the results from the cell toxicity study using fibroblastsas model cells.

FIG. 16 shows light scattering data from aqueous solutions of mixturesof C₁₆₋₁₈G₄₋₂₀ and C₁₆₋₁₈G₁₋₃. The total surfactant concentration was 2mg/ml in all experiments, and the C₁₆₋₁₈G₄₋₂₀ to C₁₆₋₁₈G₁₋₃ ratio isindicated in the figure. The y axis of the figure gives the turbidity ofthe samples, stated as the number of photons reaching the detector perunit time (referred to as “derived count rate” and given in units ofkilo-counts per second).

DETAILED DESCRIPTION

The present invention relates to unique surfactant compositions based onalkylglycosides with hydrophilic headgroups consisting of four or morerepeating saccharide units. In contrast to existing alkylglycosidecompositions, the composition described herein contains alkylglycosideswith long head-groups (n≧4) as main components. The invention alsorelates to the use of the compositions as surface-active agentsparticularly in the field of wetting particles and surfaces,emulsification and stabilisation of pharmaceuticals.

Disclosed herein is a surfactant composition comprising at least onealkylglycoside which has the formula I

C_(n)G_(m)  (I)

whereinC is an alkyl group;n is the number of carbon atoms in the alkyl group and is 14 to 24;said alkyl group being unbranched or branched, saturated or unsaturated,derivatised or non-derivatised;G is a saccharide unit containing 5 to 6 carbon atoms; andm is a number from 4 to 20.

The alkyl moiety (C in formula I) of the alkylglycosides present in thesurfactant composition according to the invention also emanatespreferably from readily available derivatives of renewable rawmaterials, more particularly from fatty alcohols, althoughbranched-chain isomers thereof may also be used for the production ofsuitable alkylglycosides. Accordingly, primary alcohols containingunbranched groups in the range C14-C20 and mixtures thereof areparticularly useful. The alkyl group may contain from 16 to 20 carbonatoms (n=16-20).

Particularly preferred surfactant compositions have alkylglycosideshaving n being 16 or 18, such as hexadecyl (straight saturated chain) oroleoyl (straight, unsaturated), or 12-hydroxystearoyl (straight,derivatised), or any combination thereof.

However, the index n may preferably be chosen from 14-22, 14-20, or16-18.

G (the head-group) in the formula is a repeating saccharide unit. Thestructure of the residue being determined by the mono, di, oroligosaccharide used as starting material. Examples of the startingmaterial for G include e.g. monosaccharides as glucose, fructose,galactose, xylose, mannose, lyxose, arabinose, and mixtures of these,and oligosaccharides as maltose, xylobiose, isomaltose, cellobiose,gentiobiose, lactose, sucrose, nigerose, turanose, raffinose,gentianose, melezitos, and mixtures of these. Particularly preferred isglucose.

The index m in the formula is a number from 4 to 20, which representsthe so-called degree of oligomerisation, i.e. the number of repeatingsaccharide units. The index m may be chosen from 4-19, 4-18, 4-17, 4-16,4-15, or 4-14. The index m may alternatively be between 5 and 20, e.g.5-19, 5-18, 5-17, 5-16, 5-15, or 5-14. The index m may alternatively bebetween 6 and 18, such as 7 and 17, and may e.g. be chosen from 7, 8, 9,10, 11, 12, 13 or 14, more preferably chosen from 7, 8, 13 or 14.

If the surfactant composition according to the present invention howevercontains alkylglykosides outside the desirable range according to thepresent invention, these may then, if present in too high amounts,contribute with a less efficient effect and thus less desirable effectof the surfactant composition. It would be preferable that the presentinvention did not contain any alkylglycoside chosen from G₁₋₃. However,if there is any alkylglycoside chosen from G₁₋₃ present in saidcomposition, it would be preferable to limit the amount to at most 33%of the alkylglycosides. Thus, according to one embodiment therelationship between G₁₋₃ and G₄₋₂₀ is preferably at most 33:67,preferably at most 30:70, preferably at most 20:80, preferably at most20:90 and preferably at most 5:95.

The longer head-group makes the surfactant composition less active as anirritant on skin and mucosa, and more benign to living cells. In otherwords, the longer head-group increases biocompatibility.

Particularly preferred alkylglycosides are such that they either

-   -   (1) contain at least one or a mixture of alkylglycosides having        m being selected from 7 to 14, preferably comprising C_(n)G₇ or        C_(n)G₈. Mixtures may e.g. contain (C_(n)G₇) and (C_(n)G₁₃), or        (C_(n)G₈) and (C_(n)G₁₄).    -   (2) contain a polydisperse mixture of components C_(n)G_(m),        having components with m=4-20 preferably representing at least        67% of the total amount of alkylglycosides present.

As an example the surfactant composition may comprise at least twoalkylglycosides which have m being 7 or 8, and 13 or 14, respectively,and preferably are chosen from C₁₆G₇, C₁₆G₈, C₁₆G₁₃ and C₁₆G₁₄, whereC₁₆ denotes a hexadecyl residue.

As another example, the surfactant composition may consist of apolydisperse mixture of G16Gn alkylglycosides. If such mixture comprisesany C₁₆G₁, C₁₆G₂ and C₁₆G₃ they preferably together represent at most33% of the mixture.

As a further example the surfactant composition may comprise at leasttwo alkylglycosides which have m being 7 or 8 and 13 or 14,respectively, and preferably are chosen from C18G7, C18G8, C18G13 andC18G14, and preferably C18 denotes an oleoyl residue or an12-hydroxystearoyl residue.

The ratio of CnG8 to CnG14, or CnG7 to CnG13, may be between 50:50 to95:5, such as 50:50 to 90:10.

G is covalently linked via a glycosidic bond to a single alkyl chaincontaining at least fourteen carbons. This class of surfactantcompositions comprise head-groups that are longer than those present inalkylglycoside products available today. Thus, surfactant compositionsaccording to the present invention address severe drawbacks of thecurrent technology, in the following ways: By making the head-groupsignificantly longer than is the case in current technology, the Krafftpoint for a given length of alkyl chain decreases, hence increasingsolubility at temperatures relevant for most applications. Since manyapplications require or benefit from long alkyl chains, this opens upthe possibility to replace current technology with surfactantcompositions according to the present invention that are much moreefficient, thus decreasing the amount required in any given application.A longer head-group also decreases the toxicity of the alkylglycoside,and lowers its tendency to act as an irritant on mucosa and othersensitive tissue.

The alkylglycosides according to the present invention exhibit highchemical stability. In addition, the surfactant composition according tothe present invention may be subjected to heat without losing itsproperties as an excellent surfactant composition. The present inventionthus provides an excellent surfactant composition that combines a lowKrafft point with high efficiency, high physical and chemical stabilityand low toxicity.

According to another embodiment, the surfactant composition consists ofone alkylglycoside according to formula I.

At concentrations above the critical micelle concentration (CMC), thepresent surfactant composition may show surface tension values at orabove CMC of at least 32 mN/m, for example at least 40 mN/m, preferablyat least 45 mN/m, such as about 42-53 mN/m, about 45-51 mN/m and about49 mN/m.

It has been discovered that the present surfactant composition displaysa very surprising behavior in terms of the relationship between itssurface activity (as defined by the surface tension at the air-waterinterface) and its wetting properties. More specifically, the highsurface tension suggest a much lower surface activity than for existingalkylglycosides and ethoxylated surfactants (e.g. polysorbate 80), yetits wetting properties are superior. The surfactant composition alsopacks in a surprisingly efficient manner when adsorbed to surfaces,which contributes beneficially to its superior wetting andemulsification properties.

The present surfactant composition may thus be used for efficientwetting of surfaces or particles, emulsification of water/oil systems,prevention of unwanted intermolecular interaction between proteins andpeptides (aggregation) and/or between said molecules and surfaces intheir environment (adsorption). The present surfactant composition andsolutions thereof are heat-stable and stable when subjected to freezingand/or thawing.

The surfactant composition is capable of providing excellent wetting anddispersion of particles of hydrophobic small organic molecules used inpharmaceutical formulations. The surfactant composition may also be usedas an emulsifier providing for an emulsion. It may also be used forincreasing the stability, reduce aggregation and immunogenicity andincrease biological activity of peptides and proteins in therapeuticallyuseful formulations.

Thus, the surfactant composition according to the invention may becomprised in a detergent composition, a wetting agent, an emulsifyingagent or in a dispersant composition.

It has been discovered that using surfactant compositions according tothe present invention, compositions comprising alkylglycosides having atleast four saccharide units result in improvement in the wettingproperties of aqueous solutions of said alkylglycosides. Also, it hasbeen surprisingly found that the use of alkylglycoside compositionsaccording to the present invention, to a higher extent reduces,prevents, or lessens peptide or protein association or aggregation of anemulsion or suspension or mixture. For example, the peptide or proteinself-association or self-aggregation is reduced. Also, the associationor aggregation with other peptides or proteins when administered to thesubject is reduced.

Furthermore, the present surfactant composition may be used in foods,beverages, pharmaceuticals, cosmetics, personal care products,detergents, cleaning agents, etc. Examples are gels, creams, lotions,tooth paste, ointments, injectabilia, nasal sprays, liquids forinhalation, eye drops, tablets, laundry detergents, wet wipes, etc.

EXAMPLES Thermal Physical Stability, Solubility and Krafft Point

Over the course of extensive studies, solutions comprising a C₁₆G_(8/14)mixture were found never to produce any precipitate, not even whenstored under refrigerated conditions (2° C.) for years. This means thatthe Krafft point of both C₁₆G₈ and C₁₆G₁₄ is below 2° C. This value iscompared with other alkylglycosides^([11,12,13]) in Table 1. Similarly,polydisperse mixtures of C₁₆₋₁₈G₄₋₂₀ were found to be soluble at roomtemperature, and not to produce a precipitate when stored underrefrigerated conditions for extended periods of time (Table 1).

In order to determine the Krafft point of a C₁₆₋₁₈G₁₋₂₀ mixture as afunction of the average head-group length, the following experiment wasconducted: By chromatography, C₁₆₋₁₈G₁₋₂₀ was split into two fractions:C₁₆₋₁₈G₁₋₃ and C₁₆₋₁₈G₄₋₂₀. The Krafft temperature of each fraction wasdetermined and found to be 35-40° C. and <2° C., respectively (Table 1).Next, C₁₆₋₁₈G₁₋₃ was blended into C₁₆₋₁₈G₄₋₂₀ in increasing amounts, andthe Krafft point determined by light scattering experiments for eachspecific mixture. The results are summarised in FIG. 16. As is evident,the light scattering intensity is constant and very low for compositionssuch that the C₁₆₋₁₈G₄₋₂₀:C₁₆₋₁₈G₁₋₃ ratio is ≧75:25. This shows thatall material is properly dissolved, and hence that the Kraffttemperature is below room temperature. However, forC₁₆₋₁₈G₄₋₂₀:C₁₆₋₁₈G₁₋₃ ratios ≦70:30, the systems need to be heated to30-40° C. before the light scattering intensity is consistent with aproperly dissolved system. Hence, the data in FIG. 16 clearlydemonstrate that C₁₆₋₁₈G₁₋₂₀ mixtures have cloud point above roomtemperatures if the short-chain fraction (C₁₆₋₁₈G₁₋₃) comprises morethan 30% of the alkylglycoside composition. As is evident from thesestudies, enlongation of the head-group dramatically decreases the Krafftpoint and enables longer alkyl chains to be used without sacrificingsolubility.

In contrast to the case of PEG-based surfactants, heating of solutionscomprising a C₁₆G_(8/14) mixture have been found not to produce phaseseparation, even at the boiling point.

TABLE 1 Krafft point of selected alkylglycosides. Surfactant Krafftpoint/° C. Reference C₁₆G_(8/14) <2 Measured for present applicationC₁₆G₂ 41 [12] C₁₄G₂ 32 [11] C₁₂G_(8/14) <2 Measured for presentapplication C₁₂G₂ <0 [11] C₁₂G₁ 38 [13] C₁₆₋₁₈G₄₋₂₀ <2 Measured forpresent application C₁₆₋₁₈G₁₋₃ 35-40 Measured for present applicationC₁₆₋₁₈G₁ (TEGO >90 Measured for present Care CG90) application

CMC and Surface Tension at the Air-Water Interface

The CMC of a surfactant composition comprising a C₁₆G_(8/14) mixture wasdetermined by means of tensiometry (FIG. 1). According to themeasurement, the CMC is 37 mg/L, which for this particular mixture isequivalent to 24 μM. This value may be compared to the correspondingvalue for the PEG-based surfactants C₁₆E₉, C₁₆E₁₂ and C₁₆E₂₁ which showCMC values of 2.1, 2.3 and 3.9 μM, respectively^([14]). The value mayalso be compared with the CMC of Polysorbate 80, at 13-15 mg/L (10-11μM)^([15]). These results confirm that a surfactant compositioncomprising a C₁₆G_(8/14) mixture is more hydrophilic, compared tosimilar PEG-based surfactants. Surprisingly, it has been found that thesurface tension of solutions of comprising a C₁₆G_(8/14) mixture atconcentrations above the CMC (49 mN/m) is significantly higher than thatof PEG-based surfactants (30-35 mN/m), and that of conventionalalkylglycosides with short head-group (32-37 mN/m)^([16]). The highsurface tension may be a key to the biocompatibility of the C₁₆G_(8/14)mixture.

Adsorption to Hydrophobic Surfaces

Ellipsometric studies of the adsorption of a C₁₆G_(8/14) mixture tohydrophobic model surfaces reveal a very efficient surface coverage,corresponding to 3 mg/m² (2 μmol/m²), FIG. 2. For comparison, theadsorption of Polysorbate 80 to hydrophobic silica substrates is 1.4mg/m² (1.1 μmol/m²) at 0.028 mg/ml^([17]). Hence, in terms of adsorbedmass, C₁₆G_(8/14) is about twice as efficient as Polysorbate 80, inspite of its lower surface activity (as determined by tensiometry; seeabove).

Cell Toxicity

The cytotoxicity of a surfactant composition comprising a C₁₆G_(8/14)mixture was evaluated and compared with a number of other surfactants atconcentrations above and below the critical micelle concentration (CMC).As parameter for cytotoxicity, cell metabolism was assessed by XTTconversion. The XTT assay is based on the mitochondrial activity of thecells and reflects on how active and thereby how viable the cellsare^([24,25]). The XTT compound (sodium3′[1-phenyl-aminocarbonyl]-3,4-tetrazolium bis[4-methoxy-6-nitro]benzene sulphonic acid hydrate) is reduced by the mitochondria and formsan orange coloured formazan dye. The colour change from yellow to orangeis measured by a spectrophotometer at 450 nm.

Fibroblasts cells seeded in 96-well plates at a cell concentrationwithin the linear region for the XTT assay were cultured for 24 hours in200 μl Dulbecco's modified Eagles's medium (DMEM) containing 10% fetalbovine serum (FBS) prior to the addition of the surfactants. The culturemedium was then removed and 200 μl of the respective surfactantsolutions was added to the wells and incubated for 1 hour. Thesurfactant solution was removed and 200 μl XTT medium was added to thewells, including blanks, and incubated for 2 hours (37° C., 5% CO₂). Theabsorbance was measured at 450 nm. The results were expressed asabsorbance observed as % of control cultures (non-treated cells). As canbe seen in FIG. 15a the cell viability is higher in the composition ofC₁₆G_(8/14) (denoted C16G8 in figure) than in both polysorbate 80 andC16G2. The concentration at which the cell viability was decreased by50% (IC50) was 0.43 mM for the C₁₆G_(8/14) composition compared to 0.13mM for polysorbate 80 and 0.017 mM for C16G2.

After the surfactant composition was removed, the cells that had beenexposed to the C₁₆G_(8/14) mixture had completely recovered after 2hours (FIG. 15b ) while a slightly less complete recovery was observedfor polysorbate 80. The cells that had been exposed to C16G2 on theother hand, did not recover at all during 2 hours.

Chemical Stability

The chemical stability of a C₁₆G_(8/14) mixture in an aqueousformulation sensitive to oxidation was compared to that of two differentgrades of Polysorbate 80 (Super-Refined and Pharma Grade). Butylatedhydroxytoluene (BHT) was used as oxidation-prone model compound. BHT iseasily oxidised to 3,3′,5,5′-tetra-bis-(tert-butyl)-stilbenequinone,which is bright yellow. 0.5 mg/ml of micronised BHT was dispersed in 150mM NaCl solution, using 0.2 mg/ml of surfactant as dispersant. Thepreparations were placed on stability at room temperature and 40° C. Theformulations were analysed by HPLC and visually inspected at regulartime points. During the course of the study, the visual inspection ofthe bottles revealed that gradual yellow discoloration was much morepronounced for the solutions containing polysorbate, which clearlyindicated a lower chemical stability of polysorbate than the C₁₆G_(8/14)mixture. The HPLC results provide quantitative conformation of thisconclusion, as displayed in FIG. 4. As is evident, a C₁₆G_(8/14) mixtureis vastly superior to the two grades of polysorbate in terms of chemicalstability of the formulation. In actual fact, over the course of the28-week study, the BHT content in the C₁₆G_(8/14) mixture system did notdecrease, even under accelerated conditions (40° C.). In the polysorbatesystems, on the other hand, BHT content was found to decreasedramatically with time.

Inhibition of Peptide and Protein Aggregation

Inhibition of peptide and protein aggregation is crucial for thephysical stability and safety, particularly for pharmaceutics forinjection (injectabilia). Therefore, surfactants are normally applied asinhibitors of peptide and protein aggregation in such formulations. Theability of a C₁₆G_(8/14) mixture to inhibit peptide and proteinaggregation in solution was investigated using insulin as model peptide.In the study, a C₁₆G_(8/14) mixture was compared with Polysorbate 20 (astandard surfactant currently approved for injectabilia), and C₁₄G₂(tetradecylmaltoside; a novel excipient purchased from Anatrace(Affymetrix) recently suggested for this application by AegisTherapeutics, see^([)21, 22]. In the study, the insulin concentrationwas 0.4 mg/ml and the surfactant concentration 1.4 mg/ml. The pH of thesolutions was buffered by citrate at either pH 6.8 (acceleratedconditions) or pH 7.4. The solutions were put on stability intriplicates at 25 and 40° C., and analysed by visual inspection after 2,4, 8, and 12 weeks. The results of the study is summarised in Table 2.As is evident, C₁₄G₂ proved unable to inhibit precipitation, even undernon-accelerated conditions. Polysorbate 20 performed considerablybetter, but did not stop precipitation at 40° C. at either pH 6.8 or pH7.4. Of the three surfactants in the study, the C₁₈G_(8/14) mixtureproved superior. For this surfactant composition, precipitation wasobserved only for the most accelerated condition (40° C., pH 6.8).

TABLE 2 Results from a study investigating the ability of Polysorbate20, C14G2 and a C₁₆G_(8/14) mixture to inhibit precipitation of insulin.Filled boxes denote systems in which a solid precipitate was observedafter a given time of storage under the conditions indicated.

Preparation of Suspensions (Dispersions; Sols)

The propensity of selected surfactant compositions to act as efficientdispersants for micronised, hydrophobic particles was tested inpharmaceutical formulations using the two steroid drugs budesonide andbeclometasonedipropionate (BDP) as model compounds. The following novelalkylglycoside compositions were included in the studies: C₁₂G_(8/14),C₁₆G_(8/14), and C₁₆₋₁₈G₄₋₂₀. These compositions were compared with theconventional alkylglycoside compositions TEGO Care CG90 (consistingmainly of C₁₆₋₁₈G₁), C₁₆₋₁₈G₁₋₃, and C₁₆G₂.

In addition, the performance of the novel compositions was compared withthat of the ethoxylated surfactant polysorbate 80 (PS80). PS80 used inthe study was of Super-Refined grade, which represents thestate-of-the-art of current technology.

The test suspensions were prepared as follows: The appropriatesurfactant was dissolved in water to a concentration of 20 mg/ml. To thebeaker containing the surfactant solution, an amount of drug powder wasadded, so that the nominal drug concentration was 50 mg/ml. The drug wasthen dispersed in the surfactant solution using either (1) high-shearmixing by means of an Ultra Turrax mixing device, or (2) low-shearmixing using a magnetic stirring bar. After 1 minute of agitation witheither of the mixing devices, the resulting suspension was transferredto a volumetric flask and diluted 100-fold by addition of 0.15 M NaCl.Consequently, the final drug concentration was 0.5 mg/ml, and the finalsurfactant concentration 0.2 mg/ml.

The two BDP suspensions containing C₁₂G_(8/14) and C₁₆G₂ weremacroscopically inhomogenous irrespective of the mode of mixing, andcontained large aggregates clearly visible by the naked eye. Visibleinspection thus proved sufficient to show that these surfactantcompositions are useless for the intended purpose, and the suspensionswere not subjected to further characterisation. The BDP suspensionscontaining C₁₆G_(8/14) and PS80, on the other hand, were found to behomogenous to the naked eye, and were therefore subjected to further,detailed analysis by laser diffraction (Malvern MasterSizer) and fastparticle image analysis (Malvern FPIA3000). As is evident from the laserdiffraction data displayed in FIG. 4, use of PS80 as dispersant underhigh-shear conditions results in a skew-symmetric particle sizedistribution, clearly indicative of aggregation. Use of a C₁₆G_(8/14)mixture, on the other hand, gives rise to a nearly perfect symmetricaldistribution with no signs of aggregation. FIG. 5 shows thecorresponding data for systems prepared by low-shear mixing. Due to thelow shear, aggregates were found to be abundant in this experiment.However, there was still a huge difference between C₁₆G_(8/14) and PS80.In the former case, the presence of aggregates is evident as ripples inthe large-size tail of the diffraction data. However, the small size ofthese ripples strongly suggests that the amount of aggregates is verylow. In the PS80 case, on the other hand, the size distribution functiondisplays a pronounced bimodality, clearly suggesting a much moreextensive aggregation. The conclusions derived from the laserdiffraction data are confirmed and extended by the data from the imageanalysis. These data (in the form of micrographs of aggregates andprimary particles, FIGS. 6-9) show that replacing PS80 with aC₁₆G_(8/14) mixture, allows for replacing high-shear mixing withlow-shear mixing, without sacrificing proper dispersion. This representsa huge advantage in a process setting, since high-shear mixing leads tosubstantial foaming, and concomitant issues pertaining to yield andreproducibility. The images displayed in FIGS. 6-9 have been selected sothat they represent a population that is statistically representative ofthe largest objects (aggregates/particles) in the systems. It isimportant to realise that the aggregates on the two cases are verydifferent: In the PS80 case, the aggregates are fractal objects ofloosely bound primary particles, whereas in the case of a C₁₆G_(8/14)mixture they are actually composed of primary particles that are fusedtogether. The former type of aggregates are possible to disperse with asufficiently active dispersant, whereas the latter are not (they stemfrom the crystallisation step in API production and are hence present inthe starting material used in preparation of the suspensions).Consequently, the images in FIGS. 6-9 provide another proof thatC₁₆G_(8/14) is a more efficient wetting agent (dispersant) than PS80.

The ability of polydisperse alkylglycoside compositions (C₁₆₋₁₈G₄₋₂₀) toact as efficient dispersants was investigated by the same experimentalprotocol, but micronised budesonide as model drug. Again, thesuspensions were characterized by means of laser diffraction.

FIGS. 10, 11 and 12 show the laser diffraction data for budesonidesuspensions containing C₁₆₋₁₈G₄₋₂₀, C₁₆₋₁₈G₁₋₃ and TEGO Care CG90(consisting mainly of C₁₆₋₁₈G₁) as dispersant, respectively. As can beseen in FIG. 10, the particle size distribution obtained when usingC₁₆₋₁₈G₄₋₂₀ as dispersant is perfectly symmetric and monomodal. Thisclearly shows that the system comprises only properly dispersed primaryparticles, and thus proves the excellent wetting properties ofC₁₆₋₁₈G₄₋₂₀. In stark contrast, the distribution obtained when usingC₁₆₋₁₈G₁₋₃ as dispersant (FIG. 11) is markedly bimodal, suggesting poorwetting and quite substantial aggregation. For TEGO Care CG90, thesituation is even worse, as shown in FIG. 12. Here, only aggregates, andno primary particles, are evident in the diffraction data. Inconclusion, the results clearly illustrate the importance of head-grouplength on surfactant performance, and also show the superiority ofalkylglycosides with more than three repeating glucose units.

Heat-Stability of Suspensions

The heat stability of suspensions prepared with a surfactant compositionaccording to the present invention was investigated by heatingsuspensions of micronised budesonide (0.5 mg/ml) to 90° C. for 30minutes on a water bath and to 125° C. for 8 minutes in an autoclave.The suspensions were prepared by high-shear mixing as previouslydescribed, using 0.2 mg/ml of a C₁₆G_(8/14) mixture as dispersant. Theparticle size distribution was investigated by means of laserdiffraction measurements. For comparison, suspensions of micronisedbudesonide were also prepared using Polysorbate 80 as dispersant.

Data on the particle size distribution for suspensions prepared usingPolysorbate 80 as dispersant are shown in FIG. 13. As is evident,heating of the suspension to 90° C. induces a substantial shift of theparticle size distribution towards higher particle size. The datademonstrate that the heat decreases the ability of Polysorbate to act asa dispersant and hence induces aggregation of primary particles. Thisobservation is entirely consistent with the general propensity ofPEG-based surfactant to phase separate at elevated temperatures,^([6])and constitute, as already alluded to, a serious drawback. Under thestill more severe conditions represented by autoclavation, theaggregation is near-complete and a visual inspection of the systemrevealed millimetre-sized chunks of aggregated budesonide that wereimpossible to re-disperse and that quickly settled in the bottom of theflask. Data on the particle size distribution for suspensions preparedusing a C₁₆G_(8/14) mixture as dispersant are shown in FIG. 14. As isevident, heating to 90° C. for 30 minutes has only minute impact on theparticle size distribution. This clearly demonstrates superiority overPolysorbate 80 in terms of heat-stability. After autoclavation, theparticle size distribution was found to shift substantially towardslarger particle size, but still in a far less dramatic way than for thesuspension prepared with Polysorbate 80. In addition, visual inspectionof the suspension prepared with a C₁₆G_(8/14) mixture revealed that thesuspension was readily re-dispersed after autoclavation, in contrast tothe suspension prepared with Polysorbate 80 as dispersant. Use of asurfactant composition according to the present invention thereforeopens the possibility to utilise autoclavation as a means ofsterilisation.

Preparation of Emulsions

In order to compare emulsion characteristics model emulsions containing1.2% emulsifier (a C₁₆G_(8/14) mixture; Polysorbate 80; or a C₁₂G_(8/14)mixture) and 20 or 50% canola oil were manufactured. An emulsifier stocksolution with a concentration of 24 mg/ml was prepared. Then, 1 ml ofthe stock solution was mixed with 0.6 ml of water and added to 0.4 mlcanola oil to produce the 20% oil emulsions. Further, 1 ml of the stocksolution was mixed with 1 ml of canola oil to produce the 50% oilemulsions. The homogenization was carried out using a SONICS, Vibracell,ultrasonic probe at 40% amplitude for 15 s, followed by a 15 s pause,for a total of 1 min active sonication. This sequence was repeated twomore times with a longer break in between repetitions to minimizetemperature fluctuations. This procedure resulted in smooth, whiteemulsions for the emulsifiers Polysorbate 80 and the surfactantcomposition comprising a C₁₆G_(8/14) mixture. Two batches of theC₁₆G_(8/14) mixture were tested and for the first two months allemulsions were stable. However, after approximately three months phaseseparation in the emulsions containing Polysorbate 80 and one of theC₁₆G_(8/14) batches had occurred. It can therefore be concluded that aC₁₆G_(8/14) mixture produces more stable emulsions than Polysorbate 80.For the C₁₂G_(8/14) mixture only half the volumes listed above were usedand still an additional 15 s of ultra-sonication at 70% amplitude wasneeded to produce smooth, white, stable (at least for three weeks)emulsions. Clearly the C₁₂G_(8/14) composition is a less effectiveemulsifier than both the C₁₆G_(8/14) composition and Polysorbate 80.

REFERENCES

-   1. K. Ekelund et al, J. Pharm. Sci. 2005, 94, 730.-   2. M. Bergh et al, Contact Dermatitis 1998, 39, 14.-   3. M. Donbrow et al, J. Pharm. Sci. 1978, 67, 1676.-   4. F. O. Ayorinde et al, Rapid Comm. Mass Spectosc. 2000, 14, 2116.-   5. B. A. Kerwin, J. Pharm. Sci. 2008, 97, 2924.-   6. B. Jönsson et al, Surfactants and Polymers in Aqueous Solution,    Wiley 1998, p. 91.-   7. R. Eskuchen et al, “Technology and Production of    Alkylglycosides”, in “Alkyl Polyglycosides—Technology, Properties    and Applications”, VCH (Weinheim), 1996-   8. WO2010097421-   9. D. Svensson et al, Biotech. Bioeng. 2009, 104, 854.-   10. D. Svensson et al, Green Chem. 2009, 11, 1222.-   11. C. A. Ericsson et al, Phys. Chem. Chem. Phys. 2005, 7, 2970.-   12. C. Hansson, Structure and Thermodynamics of Micellar    Alkylglycoside Solutions, Diploma Work, Lund University, 2001.-   13. L. Ericsson, Solid-State Phase Behaviour of Alkylglycosides,    Diploma Work, Lund University, 2005.-   14. B. Jönsson et al, Surfactants and Polymers in Aqueous Solution,    Wiley 1998, p. 38.-   15. Tween 80 Product Information Sheet, Sigma-Aldrich.-   16. C. A. Ericsson et al, Langmuir 2005, 21, 1507.-   17. S. H. Mollman et al, Pharm. Res. 2005, 22, 1931.-   18. M. J. Rosen et al, J. Surf. Detergents 1999, 2, 343.-   19. M. J. Rosen et al, Environmental Sci. Techn. 2001, 35, 954.-   20. Final Safety Assessment of Decyl Glucoside and Other Alkyl    Glycosides as Used in Cosmetics. Cosmetic Ingredient Review. Dec.    19, 2011.-   21. WO2010151703 A1-   22. EP2457580 A1-   23. M. T. Gam is et al, Chemosphere 1997, 35(3), 545-556.-   24. F.-X. Reichl et al, Archives of Toxicology, 2006, 80(6),    370-378.-   25. Scudiero, D. A., et al., Cancer Res, 1988, 48(17), 4827-4833.

1. A surfactant composition comprising at least one alkylglycosidehaving the formulaC_(n)G_(m) wherein C is an alkyl group; n is the number of carbon atomsin the alkyl group and is 14 to 24; said alkyl group being unbranched orbranched, saturated or unsaturated, derivatised or non-derivatised; G isa saccharide residue containing 5 to 6 carbon atoms; and m is a numberfrom 4 to
 20. 2. The surfactant composition according to claim 1,wherein the alkyl group comprises cyclic fractions.
 3. The surfactantcomposition according to claim 1, wherein m is between 4 and 20,preferably between 4 and 19, and preferably between 4 and
 18. 4. Thesurfactant composition according to claim 3, wherein m is between 6 and18, preferably between 7 and 17, more preferably is chosen from 7, 8, 13or
 14. 5. The surfactant composition according to claim 1, wherein n is14 to 20, preferably 14 to 18, or preferably 16 to
 18. 6. The surfactantcomposition according to claim 1, wherein m is selected from 7, 8, 13,or 14; and n is selected from 16 or
 18. 7. The surfactant compositionaccording to claim 1, wherein the surfactant composition comprises atleast two alkylglycosides having m being 7 or 8 and 13 or 14,respectively.
 8. The surfactant composition according to claim 7,wherein the ratio between (C_(n)G₈) to (C_(n)G₁₄) or (C_(n)G₇) to(C_(n)G₁₃) is about 50:50 to 95:5.
 9. The surfactant compositionaccording to claim 1, wherein said at least one alkylglycoside has asurface tension value at or above critical micelle concentration (CMC)of at least 32 mN/m, preferably of at least 40 mN/m, preferably 42-49mN/m, preferably about 45-49 mN/m, such as about 47 mN/m.
 10. Detergentcomposition comprising the surfactant composition according to claim 1.11. A wetting agent comprising the surfactant composition according toclaim
 1. 12. An emulsifying agent comprising the surfactant compositionaccording to claim
 1. 13. Dispersant composition comprising thesurfactant composition according to claim
 1. 14. Anti-aggregation andstabilising composition comprising biomolecules and the surfactantcomposition according to claim
 1. 15. Method of using the surfactantcomposition according to claim 1 as a detergent, a wetting agent, anemulsifying agent, anti-aggregation agent or a dispersant.
 16. Method ofusing the surfactant composition according to claim 1 in foods,beverages, pharmaceuticals, cosmetics, personal care products,detergents or cleaning agents.